Does Chemotherapy Change Expression of VEGF A&C and MVD in Acute Myeloid Leukemia?

INTRODUCTION: Acute Myeloid Leukemia is a malignant transformation of hematopoietic tissue, bone marrow infiltration of undifferentiated cells known as blasts that interfere with the production of normal cells. Vascular endothelial growth factor (VEGF) is persistently secreted from myeloid cells and high levels can be detected in patients' serum. METHODS: Twenty-one AML patients, who were chemotherapy candidates were evaluated in a clinical trial. Serum VEGF was measured by ELISA. VEGFA, VEGFC mRNA and bone marrow MVD were measured in all patients before and after chemotherapy and then all results were analyzed. RESULTS: There were 10 (48%) female and 11(52%) male patients ranged in age from 20 to 60 years, with an average age of 39.5 ±14.1 years. The mean amount of MVD was reduced from 10.8±3.6 before chemotherapy to7.6±3.3 after chemotherapy (P=0.008). VEGF was also reduced from 0.59±0.16 before chemotherapy to 0.24±0.03 after chemotherapy (P=0.005). Gene expression differences for VEGFA mRNA was 4.6±1.4, while it was 120.7±93.2 for VEGFC mRNA, showing the significance only for VEGA mRNA (P=0.02). CONCLUSION: Regarding reduced angiogenesis, we can conclude that anti-angiogenic preparations can be effective in treatment course of AML in combination with chemotherapy regimen.

Gene Expression of VEGF-A and VEGF-C in Peripheral Blood Mononuclear Cells of Iranian Patients with Acute Myeloid Leukemia.

OBJECTIVE: The crucial role of angiogenesis in the pathophysiology of acute myeloid leukemia (AML) has been proposed. One of the key regulators of angiogenesis is the vascular endothelial growth factor (VEGF). Among the VEGF family, it has been observed that VEGF-A and VEGF-C are expressed by AML cells and mediate leukemic cell proliferation, survival, and resistance to chemotherapy. Emerging evidence, however, suggests that elevated levels of VEGF or a proangiogenic phenotype may impede, rather than promote, early tumor development and progression. As the significance of VEGF-A and VEGF-C levels in the pathogenesis of AML has not been clarified well, the aim of this study is to evaluate gene expression of these angiogenesis promoters and its possible prognostic value in peripheral blood mononuclear cells of Iranian patients with AML. MATERIALS AND METHODS: We investigated the mRNA expression of VEGF-A and VEGF-C in peripheral blood mononuclear cells of 27 patients with newly diagnosed AML and 28 healthy controls by quantitative real-time PCR. RESULTS: Expression of VEGF-C mRNA was significantly lower in AML patients than in healthy controls (p<0.001). However, there was no significant decrement in expression of VEGF-A mRNA of AML patients compared to the control group (p=0.861). VEGF-A and VEGF-C expression were not able to predict clinical outcome. CONCLUSION: Our data showed that AML is associated with a decreased expression of VEGF-C mRNA. However, expression levels did not influence the clinical outcome in our study. It seems that angiogenesis is affected by different cytokines other than VEGF-C or VEGF-A, and VEGF is also affected by different cytokines. Taken together, these findings help to provide new insights into the investigation of other angiogenic factors and cytokines that may play roles in the pathogenesis of AML. CONFLICT OF INTEREST: None declared.

Study of apoptosis in labeled mesenchymal stem cells with superparamagnetic iron oxide using neutral comet assay.

Mesenchymal stem cells (MSC) have special characteristics such as migration into the damaged tissues and undergoing differentiation. One of the ways for tracking MSC in the tissue is labeling cells by contrast agents such as superparamagnetic iron oxide (SPIO) and detection by magnetic resonance imaging (MRI). To study adverse effects of SPIO on labeled cells, the formation of apoptosis in labeled cells was investigated using the comet assay. MSC were grown in vitro and labeled with various doses of SPIO for various time intervals. Incorporation of iron in cells were verified both microscopically and atomic absorption spectrophotometer. Labeled cells in a sandwich of low and normal melting agarose on slides were subjected to electrophoresis. The slides were stained with ethidium bromide and analysed under a fluorescent microscope. Results show that SPIO at various doses (50-250 microg/mL) in conjunction with protamine sulphate, used as a cationic transfection agent; and treatment times of 24-72 h did not statistically affect the frequency of apoptosis in labeled MSC (p>0.05). These findings therefore, may be indicative that labeling stem cells using these agents should facilitate the translation of this method to clinical trials for evaluation of trafficking of infused or transplanted cells by MRI.